A Fasting Population Exhibits Lower COVID-19 Severity and Mortality
Researchers here report that an epidemiological study population that practices long term intermittent fasting suffered a lesser severity and lower mortality rate in the early stages of the COVID-19 pandemic. The SARS-CoV-2 virus produces mortality via runaway inflammatory signaling, and people with a greater burden of chronic inflammation, such as through age or obesity, are less resilient. Intermittent fasting lowers inflammatory signaling, but it also produces a range of other benefits that improve resistance to infection. Further, it may be the case that the ability to fast on a schedule for decades selects for people who are more conscientious and health-minded, and who better cope with infectious disease of all sorts as a result - but the biochemistry is certainly interesting.
Fasting modifies energy utilisation by consuming glucose and glycogen, inducing gluconeogenesis, and subsequently activating ketogenesis. In the switch to ketosis during fasting, circulating levels of fatty acids, including linoleic acid, increase. Intriguingly, linoleic acid tightly binds to the spike protein of SARS-CoV-2, the cause of COVID-19. The attachment of linoleic acid to the spike reduces the affinity of SARS-CoV-2 for ACE2. An acute rise in linoleic acid while a person is fasting, thus, provides a direct mechanism for fasting to acutely reduce the severity of COVID-19.
In terms of chronic protection from severe outcomes of infection, the multifaceted protein galectin-3 was increased, independent of weight change, by low-frequency intermittent fasting in the 6-month Weekly One-Day Water-only Fasting Interventional (WONDERFUL) Trial. Galectin-3 modulates inflammation with proinflammatory actions during acute infection and anti-inflammatory functions when infection resolves. It minimises risk from chronic metabolic disorders (eg, diabetes), and is elevated in patients with diabetes and heart failure (HF), perhaps as a protective mechanism to reduce risk. Importantly, galectin-3 directly binds to a wide variety of pathogens, activates the innate immune system, impacts respiratory infections, increases expression of human genes encoding proteins with antiviral capacities and inhibits viral replication. Given the wide array of pathogens affected by galectin-3, it may also limit SARS-CoV-2 infection. The chronic increase of galectin-3 by intermittent fasting may, thus, provide a mechanistic link in which long-term participation in fasting could reduce COVID-19 severity.
Previously, routine periodic fasting was associated with lower risk of coronary artery disease (CAD), lower risk of type 2 diabetes, and - in patients with a more than 42-year history of fasting - improved longitudinal outcomes including greater survival and lower risk of incident HF. These associations may result from various mechanisms not related to weight loss. Such risk reductions by fasting of diagnoses that exacerbate the severity of COVID-19 (eg, diabetes, CAD and HF) may indirectly reduce COVID-19 severity, providing a possible third biological mechanism for fasting-induced protection from severe COVID-19 outcomes.